Temporal Coordination of Gene Networks by Zelda in the Early Drosophila Embryo

By C. Nien, Hsiao-Lan Liang, Stephen Butcher, Yujia Sun, Shengbo Fu, Tenzin Gocha, N. Kirov, J. Robert Manak, C. Rushlow. 2011

252 citations recorded by the source corpus.

In past years, much attention has focused on the gene networks that regulate early developmental processes, but less attention has been paid to how multiple networks and processes are temporally coordinated. Recently the discovery of the transcriptional activator Zelda (Zld), which binds to CAGGTAG and related sequences present in the enhancers of many early-activated genes in Drosophila, hinted at a mechanism for how batteries of genes could be simultaneously activated. Here we use genome-wide binding and expression assays to identify Zld target genes in the early embryo with the goal of unraveling the gene circuitry regulated by Zld. We found that Zld binds to genes involved in early developmental processes such as cellularization, sex determination, neurogenesis, and pattern formation. In the absence of Zld, many target genes failed to be activated, while others, particularly the patterning genes, exhibited delayed transcriptional activation, some of which also showed weak and/or sporadic expression. These effects disrupted the normal sequence of patterning-gene interactions and resulted in highly altered spatial expression patterns, demonstrating the significance of a timing mechanism in early development. In addition, we observed prevalent overlap between Zld-bound regions and genomic “hotspot” regions, which are bound by many developmental transcription factors, especially the patterning factors. This, along with the finding that the most over-represented motif in hotspots, CAGGTA, is the Zld binding site, implicates Zld in promoting hotspot formation. We propose that Zld promotes timely and robust transcriptional activation of early-gene networks so that developmental events are coordinated and cell fates are established properly in the cellular blastoderm embryo.

Subfields: Molecular Biology

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Citations in the corpus

Establishment of regions of genomic activity during the Drosophila maternal to zygotic transition (2014, background): “Although the Drosophila cellular blastoderm is among the most wellcharacterized animal tissues, the transition from quiescent to active state that precedes the formation of this tissue remains poorly understood, despite increasing evidence of its importance (Liang et al., 2008; Blythe et al., 2010; ”
Zelda potentiates morphogen activity by increasing chromatin accessibility (2014, unknown): “Experiments in Drosophila and zebrafish have revealed that ZGAdepends on transcription factors that provide large-scale control of gene expression by direct and specific binding to gene regulatory sequences [1–5].”
Impacts of the ubiquitous factor Zelda on Bicoid-dependent DNA binding and transcription in Drosophila (2014, methodology): “Previous work suggested that Zld and Bcd each binds to thousands of sites during early development (Li et al. 2008; Harrison et al. 2011; Nien et al. 2011).”
Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo (2015, background): “1C; Harrison et al. 2011; Nien et al. 2011).”
Modification of enhancer chromatin: what, how and why? (2013, background): “Unlike other TFs, Zelda can access the majority of its potential binding motifs throughout the genome and create competency for other factors to bind DNA, although the mechanism through which it does so is still unclear (Harrison et al., 2011; Nien et al., 2011).”